Target name

O60674: Tyrosine-protein kinase JAK2

  Protein function

Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.

  Database links

Uniprot primary ID O60674
PDB ID 3TJC 5CF6 4YTC 4F08 4F09 4GMY 5CF8 3LPB 3FUP 3IO7 3E62 3E63 4YTF 3E64 4JI9 4YTH 5CF4 3RVG 4YTI 3TJD 3UGC 3JY9 4HGE 4C61 4C62 4D0X 4D1S 4IVA 3ZMM 4BBE 4BBF 3Q32 4GFM 3KCK 4AQC 4ZIM 2B7A 2W1I 4FVP 4FVQ 4FVR 4E6Q 4JIA 2XA4 3IOK 5CF5 4E4M 4E6D 4P7E 5AEP 3KRR
DrugBank ID DB08877 DB08895
BioGrid ID 109920
PharmGKB ID PA29989
KEGG ID hsa:3717
STRING ID 9606.ENSP00000371067
IntAct ID O60674
Reactome R-HSA-1059683 R-HSA-392451 R-HSA-982772 R-HSA-114604 R-HSA-912526 R-HSA-2586552 R-HSA-1433557 R-HSA-1170546 R-HSA-112411 R-HSA-877312 R-HSA-877300 R-HSA-512988 R-HSA-3214858 R-HSA-983231 R-HSA-110056 R-HSA-5673000 R-HSA-5673001
SignaLink O60674
Entrez Gene (Gene ID) 3717
BindingDB O60674

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.820 0.000 0.816 0.005 0.818 0.004 0.820 0.000 0.890 0.000 0.634 0.005 Download
Estate fingerprints 0.798 0.004 0.706 0.000 0.752 0.004 0.762 0.004 0.830 0.000 0.511 0.006 Download
MACCS fingerprints 0.809 0.003 0.753 0.003 0.781 0.003 0.790 0.000 0.860 0.000 0.567 0.005 Download
Daylight fingerprints 0.810 0.000 0.770 0.004 0.790 0.000 0.794 0.005 0.838 0.004 0.582 0.004 Download
ECFP2 fingerprints 0.878 0.004 0.842 0.005 0.860 0.000 0.860 0.000 0.940 0.000 0.713 0.005 Download
ECFP4 fingerprints 0.841 0.003 0.927 0.004 0.884 0.005 0.880 0.000 0.950 0.000 0.773 0.005 Download
ECFP6 fingerprints 0.828 0.004 0.952 0.003 0.890 0.000 0.884 0.005 0.940 0.000 0.790 0.005 Download

  Download datasets

Positive dataset Negative dataset

Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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